Differential Requirement for CD4 Help in the Development of an Antigen-Specific CD8+ T Cell Response Depending on the Route of Immunization

Previous studies in our laboratory have shown that DBA/2 mice injected i.p. with syngeneic P815 tumor cells transfected with the HLA-CW3 gene (P815-CW3) showed a dramatic expansion of activated CD8 + CD62L − T cells expressing exclusively the Vβ10 segment. We have used this model to study the regulatory mechanisms involved in the development of the CW3-specific CD8 + response, with respect to different routes of immunization. Whereas both intradermal (i.d.) and i.p. immunization of DBA/2 mice with P815-CW3 cells led to a strong expansion of CD8 + CD62L − Vβ10 + cells, only the i.d. route allowed this expansion after immunization with P815 cells transfected with a minigene coding for the antigenic epitope CW3 170–179 (P815 miniCW3). Furthermore, depletion of CD4 + T cells in vivo completely abolished the specific response of CD8 + CD62L − Vβ10 + cells and prevented the rejection of P815-CW3 tumor cells injected i.p, whereas it did not affect CD8 + CD62L − Vβ10 + cell expansion after i.d. immunization with either P815-CW3 or P815 miniCW3. Finally, the CW3-specific CD8 + memory response was identical whether or not CD4 + T cells were depleted during the primary response. Collectively, these results suggest that the CD8 + T cell response to P815-CW3 tumor cells injected i.p. is strictly dependent upon recognition of a helper epitope by CD4 + T cells, whereas no such requirement is observed for i.d. injection.